Patients with HIV commonly use herbal products and dietary supplements in addition to medications prescribed by their physicians. Up to 73% of patients with HIV have reported using some form of complementary or alternative medicine. As such, the potential for clinically significant drug interactions between herbs and antiretrovirals is becoming increasingly appreciated. Despite this awareness, little is known about the effect of commonly used herbal products, such as echinacea, ginkgo biloba, and ginseng, on antiretroviral pharmacokinetics. Interacting herbal supplements have the potential to alter protease inhibitor (PI) plasma concentrations, as has been shown with St. John?s wort and garlic. Drug interactions may potentially increase antiretroviral concentrations, putting patients at risk for toxicities, or lower drug concentrations, putting patients in jeopardy of antiretroviral failure. The protease inhibitors lopinavir and ritonavir both rely principally on cytochrome P450 (CYP) 3A4 metabolism for their elimination. In addition, both drugs are both substrates for the transport protein p-glycoprotein (P-gp), which may also contribute to their distribution and elimination. [unreadable] [unreadable] The primary purpose of this investigation is to determine whether the herbal supplements Echinacea purpurea, ginkgo biloba, and Panax ginseng alter the pharmacokinetic properties of the HIV protease inhibitor combination lopinavir/ritonavir (LPV/r). Secondary objectives will assess the influence of E. purpurea, G. biloba, and P. ginseng on (1) CYP3A enzyme activity and (2) P-gp mediated drug transport. This is an open label pharmacokinetic study that will be performed on an outpatient basis. A total of 42 study participants who have met inclusion criteria will be sequentially divided into one of 3 groups, such that 14 subjects each will receive LPV/r alone and in combination with either E. purpurea, G. biloba, or P. ginseng. Subjects will receive single oral doses of fexofenadine 120 mg and midazolam 8 mg followed by plasma collection for determination of baseline CYP3A and P-gp phenotypes (Study Day 1). Between 7 and 28 days after Day 1, subjects will begin taking LPV/r (400mg/100mg twice daily x 29.5 days), returning to clinic on Day 15 of LPV/r for post-dose plasma collection and determination of lopinavir and ritonavir concentrations. On Day 16 participants will begin taking either E. purpurea (800 mg, twice daily), G. biloba extract (120 mg, twice daily), or P. ginseng (500 mg, three times daily) for 28 days. On the 30th day of LPV/r (Day 15 of the herb), subjects will return to clinic where they will take their final LPV/r dose and then have their plasma collected for determination of lopinavir and ritonavir concentrations. On the last day (28th day) of herbal supplementation, participants will return to the clinic for determination of P-gp and 3A phenotypes using single doses of fexofenadine and midazolam as described for Study Day 1. Data from this investigation will determine whether echinacea, ginseng, or ginkgo biloba supplements alter the pharmacokinetics of the protease inhibitor combination lopinavir/ritonavir, and whether or not modulation of CYP3A and/or P-gp contributed to any observed interaction.[unreadable] [unreadable] As of September, 2006, all 14 subjects have enrolled and completed the ginkgo biloba arm of the study. Pharmacokinetic data from these individuals will be available shortly.